Lambuk Lidawani, Mohd Lazaldin Mohd Aizuddin, Ahmad Suhana, Iezhitsa Igor, Agarwal Renu, Uskoković Vuk, Mohamud Rohimah
Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia.
Department of Biosciences, Faculty of Science, Universiti Teknologi Malaysia, Johor, Malaysia.
Front Pharmacol. 2022 May 20;13:875662. doi: 10.3389/fphar.2022.875662. eCollection 2022.
Retinal ganglion cells (RGCs) are neurons of the visual system that are responsible for transmitting signals from the retina to the brain the optic nerve. Glaucoma is an optic neuropathy characterized by apoptotic loss of RGCs and degeneration of optic nerve fibers. Risk factors such as elevated intraocular pressure and vascular dysregulation trigger the injury that culminates in RGC apoptosis. In the event of injury, the survival of RGCs is facilitated by neurotrophic factors (NTFs), the most widely studied of which is brain-derived neurotrophic factor (BDNF). Its production is regulated locally in the retina, but transport of BDNF retrogradely from the brain to retina is also crucial. Not only that the interruption of this retrograde transport has been detected in the early stages of glaucoma, but significantly low levels of BDNF have also been detected in the sera and ocular fluids of glaucoma patients, supporting the notion that neurotrophic deprivation is a likely mechanism of glaucomatous optic neuropathy. Moreover, exogenous NTF including BDNF administration was shown reduce neuronal loss in animal models of various neurodegenerative diseases, indicating the possibility that exogenous BDNF may be a treatment option in glaucoma. Current literature provides an extensive insight not only into the sources, transport, and target sites of BDNF but also the intracellular signaling pathways, other pathways that influence BDNF signaling and a wide range of its functions. In this review, the authors discuss the neuroprotective role of BDNF in promoting the survival of RGCs and its possible application as a therapeutic tool to meet the challenges in glaucoma management. We also highlight the possibility of using BDNF as a biomarker in neurodegenerative disease such as glaucoma. Further we discuss the challenges and future strategies to explore the utility of BDNF in the management of glaucoma.
视网膜神经节细胞（RGCs）是视觉系统中的神经元，负责将视网膜的信号传输至大脑——视神经。青光眼是一种视神经病变，其特征是RGCs凋亡性丧失和视神经纤维变性。眼内压升高和血管调节异常等风险因素引发损伤，最终导致RGCs凋亡。在发生损伤时，神经营养因子（NTFs）有助于RGCs存活，其中研究最广泛的是脑源性神经营养因子（BDNF）。其产生在视网膜局部受到调节，但BDNF从大脑逆向运输至视网膜也至关重要。不仅在青光眼早期已检测到这种逆向运输的中断，而且在青光眼患者的血清和眼液中也检测到BDNF水平显著降低，这支持了神经营养剥夺可能是青光眼性视神经病变机制的观点。此外，包括给予BDNF在内的外源性NTF已显示可减少各种神经退行性疾病动物模型中的神经元损失，这表明外源性BDNF可能是青光眼的一种治疗选择。当前文献不仅对BDNF的来源、运输和靶位点提供了广泛见解，还对细胞内信号通路、影响BDNF信号传导的其他通路及其广泛功能进行了阐述。在本综述中，作者讨论了BDNF在促进RGCs存活方面的神经保护作用及其作为应对青光眼治疗挑战的治疗工具的可能应用。我们还强调了将BDNF用作青光眼等神经退行性疾病生物标志物的可能性。此外，我们讨论了探索BDNF在青光眼治疗中的效用所面临的挑战和未来策略。
